The studies described in this proposal are designed to provide information about the molecular pathology of bacterial lipopolysaccharide (LPS)-induced pathologic changes in experimental animals. We will utilize radioiodinated LPS of high specific activity to study the interactions of LPS with cells and plasma proteins of the host. The pathogenic significance of these interactions will be evaluated by several distinct experimental approaches: (1) The kinetics and specificity of LPS interactions in the host will be correlated with development of pathologic and physiologic changes. (2) the interactions of biologically active and inactive LPS with host components will be compared. (3) The production of potentially injurious mediators by cells identified as specific targets of LPS will be studied. A molecular understanding of the mechanism of detoxification of LPS by plasma components will also result from the proposed studies.